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[Display omitted] • Prostate SBRT with an integrated focal boost demonstrated excellent 5-year outcomes. • The 5-year bDFS is comparable to that of the focal boosted FLAME-cohort. • Prostate SBRT with an iso -toxic focal boost has low rates of late toxicity. The addition of an integrated focal boost to the intraprostatic lesion is associated with improved biochemical disease-free survival (bDFS) in patients with intermediate- and high-risk prostate cancer (PCa) in conventionally fractionated radiotherapy. Furthermore, whole gland stereotactic body radiotherapy (SBRT) demonstrated to be non-inferior to conventional radiotherapy for low- and intermediate-risk PCa. To investigate the combination of ultra-hypofractionated prostate SBRT with iso-toxic focal boosting for intermediate- and high-risk PCa, we performed the hypo-FLAME trial. Patients with intermediate- or high-risk PCa were enrolled in the phase II hypo-FLAME trial. All patients were treated with 35 Gy in 5 weekly fractions to the whole prostate gland with an iso-toxic integrated boost up to 50 Gy to the multiparametric MRI-defined tumor(s). If the dose constraints to the normal tissues would be exceeded, these were prioritised over the focal boost dose. The current analysis reports on the 5-year bDFS, late toxicity and health-related quality of life (HRQoL). Between 2016 and 2018, 100 men were treated with a median follow-up of 61 months. The estimated 5-year bDFS (95 % CI) was 93 % (86 % to 97 %). At 5 years, the prevalence of grade 2 + genitourinary and gastrointestinal toxicity was 12 % and 4 %, respectively. Ultra-hypofractionated focal boost SBRT is associated with encouraging biochemical control rates up to 5-year follow-up in patients with intermediate- and high-risk PCa. Furthermore, prostate SBRT with iso-toxic focal boosting is associated with acceptable late genitourinary and gastrointestinal toxicity rates. [ABSTRACT FROM AUTHOR]

Purpose: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model.Methods and Materials: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans.Results: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86).Conclusions: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans. [ABSTRACT FROM AUTHOR]

• Focal intraprostatic lesion SBRT boosting is associated with low acute toxicity. • No acute grade ≥3 toxicity was reported in the phase II hypo-FLAME trial. • SBRT for PCa is attractive to both patients and radiation oncology departments. Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy. Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity. Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively. Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity. [ABSTRACT FROM AUTHOR]

• The overall treatment time of focal boosted prostate SBRT can safely be reduced. • No acute grade ≥3 toxicity was reported for the semi-weekly (hypo-FLAME 2.0) schedule. • Less grade 2 GU toxicity was found for the once- compared to the semi-weekly schedule. • Patients should be counselled about short-term benefits of a protracted schedule. The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To investigate the effect of an endorectal balloon (ERB) on anal wall (Awall) and rectal wall (Rwall) doses in high-dose post-prostatectomy intensity-modulated radiotherapy (IMRT). Materials and methods: For 20 patients, referred for salvage IMRT after prostatectomy for prostate cancer, two planning CT-scans were performed: one with and one without an air-filled ERB. A planning target volume (PTV) was defined, using international guidelines. Furthermore, the Awall and Rwall were delineated. In both the scans, IMRT plans were generated with a prescribed dose of 70Gy. The mean dose (D mean), maximum dose, minimum dose, and volumes exposed to doses ranging from ⩾20 to ⩾70Gy (V 20–V 70) to the Awall and Rwall were calculated. Finally, inner Rwall surface areas exposed to doses ranging from ⩾20 to ⩾70Gy (A 20–A 70) were calculated. Dose-parameters were compared between plans with and without ERB. Results: All Awall parameters, except V 70, were significantly reduced by the ERB with an overall D mean reduction of 6Gy. Absolute reductions in dose–volume parameters varied from 5% to 11%. Significantly reduced Rwall V 30, V 40, and A 40 were observed with ERB, irrespective of the target volume size. Conclusion: ERB application significantly reduces Awall and to a lesser degree Rwall doses in high-dose post-prostatectomy IMRT. [Copyright &y& Elsevier]

Abstract: Background and purpose: To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer. Materials and methods: In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D min), maximum dose (D max), and mean dose (D mean) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from ⩾20Gy to ⩾70Gy (V 20 − V 70, respectively). Results: In the 3D-CRT plans, an ERB significantly reduced D mean, D max, and V 30 − V 70. For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D mean was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Conclusions: Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy. [Copyright &y& Elsevier]